Exercise 4: Solutions

Transport in Biological Systems

Fall 2015

1. We have two-layer blood vessel with an inner radius, Ri , an outer radius, Ro , and an interface radius
of R1 ; diffusion coefficients D1 and D2 ; and solute of concentrations Ci and Co . We are asked what
the effective diffusion coefficent is.
(a) As a blood vessel is most like a hollow cylinder, and assuming steady state and no reaction given
the problem statement, we start with Ficks law,
dC 1 d  dC 
=D r = 0,
dt r dr dr

and then integrate twice, using A and B as integration constants, to get

dC A
=
dr r
C = B + Aln(r).

This solution generally holds for both the inner portion (lets use C1 ) and the outer portion
(lets use C2 ).
(b) Assuming 1 = 2 , our boundary conditions are :

C1 (Ri ) = Ci
C2 (Ro ) = Co
C1 (R1 ) = C2 (R1 )
dC1  dC2 
D1  = D2
dr R1 dr R1


(c) Then we can use these (and substitute) to solve for B1 and B2 :

B1 = Ci A1 ln(Ri )
B2 = Co A2 ln(Ro )

And we can plug that into the third boundary condition (continuous concentration) to get a
first expression for A1 :

Ci + A1 ln(R1 /Ri ) = Co + A2 ln(R1 /Ro )

Co Ci + A2 ln(R1 /Ro )
A1 =
ln(R1 /Ri )

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 Plugging that back into the continuous flux boundary condition, we can say
 C C + A ln(R /R )  D A2 D 2
o i 2 1 o 1
=
ln(R1 /Ri ) R1 R1

And after a fair bit of rearrangment, we get:

D1 (Co Ci )
A2 =
D2 ln(R1 /Ri ) D1 ln(R1 /Ro )
D2 (Co Ci )
A1 =
D2 ln(R1 /Ri ) D1 ln(R1 /Ro )

Which finally gives us:

 D2 (Co Ci ) 
C1 (r) = Ci + ln(r/Ri )
D2 ln(R1 /Ri ) D1 ln(R1 /Ro )
 D1 (Co Ci ) 
C2 (r) = Co + ln(r/Ro )
D2 ln(R1 /Ri ) D1 ln(R1 /Ro )

(d) But then the big question is what do we do with that to get an effective diffusivity? Recalling
that for a single cylinder (rearranging equation 6.7.37 from example 6.7) we can say that,
D C C 
out in
Nsingle cylinder =
ln(Rout /Rin ) r
where the first term is going to be our template for an effective diffusivity:
h D i
ln(Rout /Rin ) ef f ective

We can look at our equation for flux in the double cylinder

D 2 A2 D1 D2 (Co Ci )
Ni = No = =
r (D2 ln(R1 /Ri ) D1 ln(R1 /Ro ))r

and rearrange it to get something that looks like the single cylinders second term with some
other stuff that will be our effective diffusivity term:
D1 D2 C C 
o i
Ni = No =
D2 ln(R1 /Ri ) D1 ln(R1 /Ro ) r

So we want something that looks like an effective diffusivity... flip over that section and we can
see that it is like adding resistors in parallel:
h ln(R /R ) i ln(R1 /Ri ) ln(Ro /R1 )
out in
= +
D ef f ective D1 D2

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 where we can (probably) generalize this for n layers:
n
h ln(R
out /Rin )
i X (ln(Rout,i /Rin,i ))
=
D ef f ective Di
i=1

The point being that if we know something about the overall geometry and the concentration
difference, we can measure the effective diffusivity and then back out individual diffusivities.
Note that if D1 = D2 , we get back the original solution for 1 layer from Example 6.7. This
should look familiar from our previous 2 membrane problem and it may seem like a lot of
algebreic manipulation to get here, but this sort of solution is very powerful when you start
adding new layers. Now that we have this general form, we should know what to do if we want
to add another layer or so...
2. Considering drug delivery from a sphere (e.g. all those microsphere drugs on the market) and testing
the idea that we can neglect polymer erosion...
(a) From example 6.8, we  learned that the release rate of drug in a non-eroding sphere was
flux*surface area, Ni  (4R2 ) (equation 6.7.49). If we now consider polymer, we can assume

R
that will be similar, Np  (4R2 ), where p denotes polymer and i denotes drug. Note that these

R
expressions are the change in material per time. Well come back to the flux.
Keeping in mind that R is now R(t), and taking the volume of a sphere, V = 43 R3 , we can first
write an expression for the changing volume of the polymer sphere in time,

dV 4 d(R3 )
= .
dt 3 dt

If we multiply this by the concentration of solid polymer, we get change in material per time.
Thus we can write the relationship between the change in geometry to the release rate,

4 d(R3 ) 
Cp = Np  (4R2 ),

3 dt R
d(R3 ) 
Cp = 3R2 Np  .

dt R

and we have completed our first task! (Note that the negative sign is introduced as we equate
loss of material with flux away in the positive r direction.)
(b) Coming back to the flux, we have assumed steady state diffusion of polymer into the solvent
(note that we are now in the solvent around the polymer), we can say that, as in Example 6.8:

dCp
0= = 2 Cp
dt
1 d  2 dCp,s 
0= 2 r
r dr dr
A
Cp,s = B
r

Where concentration of the polymer in the solvent is Cp,s and B and A are integration constants.
Then we need to apply the boundary conditions. We are given the familiar Cp,s (R) = p Cp ,
where p is the partition coefficient of polymer going between the solid state and into the

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 solvent. We have discussed that a common boundary condition is Cp,s () = 0 and it appeared
in Example 6.8. Applying these, we can say that B = 0 and A = p Cp R. Thus,

p Cp R
Cp,s (r) =
r
dCp,s Dp,s p Cp R
Np,s (r) = Dp,s =
dr r2
Dp,s p Cp
Np,s (R) =
R

Dp,s is the diffusion coefficient for polymer in solvent. Recall that R is a function of t and note
that we are assuming steady state of the polymer concentration profile in the solvent is reached
faster than R changes.
(c) So now we can put everything together from the previous sections to get the change in R with
time (also known as solving Equation 6.12.4):
 
Np,s  = Np 
 
R R
Dp,s p Cp Cp 3
d(R )
= 2
R 3R dt
d(R3 )
= 3RDp,s p
dt

It may be useful to let u = R3 and then we can say that u1/3 du = 32 u2/3 in order to conclude
R

that u2/3 = R2 . So finally we can do some rearrangement and substitution and integrate from
the initial condition, R(0) = R0 , to the current condition, R(t), we can solve for R(t):

R Z t
d(R3 )
Z
d(R3 ) = 3Dp,s p dt
R0 R 0
3 2
(R R02 ) = 3Dp,s p t
2 q
R(t) = R02 2Dp,s p t

We are given a bunch of parameters

Property Polymer drug
D (cm2 /s) 1x1010 2x106
Solution solubility (mol/cm3 ) Cp,s (R) = 1x1010 C0 = 1x106
Concentration (mol/cm3 ) Cp = 1x108 Cd = 1x107
Partition Coefficient p = 0.01 d = 1.00
So, for a polymer sphere with a 0.25 cm initial radius, we can calculate that it would take
(R02 /2Dp,s p ) = 3.13x1010 s or 990 years for the polymer to completely disolve! Or it would take
about 20 years for a 1% change in diameter. We can use this information to finally think about
whether it was a good assumption to neglect degradation (quasi-steady-state assumption!).
What are the relevant timescales for drug then? From example 6.8, the drug release rate was
4Di Co R, where Di is the diffusivity of the drug and Co was the surface concentration, which we

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 are told is 106 mol/cm3 . We can calculate the total number of moles from (4/3)R03 Cinitial =
6.54x109 , where R(0) = R0 = 0.25 cm.
The release rate multiplied by time is the amount released, so we can say that:

3Di Co R(t)t
f raction drug released =
Cinitial R0

Assuming for a minute that the radius of the polymer doesnt change (using R(t) = R0 ), we can
calculate that all of the drug will be released in 1.67x104 s. Similarly, it would take 27.8 minutes
for 10% of the drug to be released! Given that all of the drug will be released LONG before a
1% change in radius, I think the assumption was good! (Though that was a long process to get
there!)
3. Considering a gap in the endothelium with a hemi-spherical profile with radius, b. We neglect the
thickness of the endothelium and consider the semi-infinite hemisphere of underlying tissue. We are
considering the transport of cholesterol in the tissue where it enters only at the damaged point (not
through the endothelium). At r = b, P = P0 and C = Cp . As r , P = 0 and C = 0. We are
asked what distributions of C, P , and v are at steady state.
(a) We start with a solute mass balance, a momentum balance in the form of Darcys law, and a
fluid mass balance:
2 dC D d  2 dC 
vC = D C v = 2 r
dr r dr dr
dP
v = KP v = K
dr
1 d  dP 
v = 0 2 P = 0 2 r2 =0
r dr dr

Where D is the diffusion coefficient and K is the hydraulic permeability.

(b) First we integrate and apply boundary conditions for the pressure to get the velocity:
a2 b
P = a1 P = P0
r r
KP0 b
v=
r2

Where a1 and a2 were integration constants equal to 0 and P b . Ok, done with the pressure
0

and velocity. That was relatively easy. But the solute concentration will do us in.
(c) Then we turn to the solute equation, substituting in our equation for velocity we can write:
KP0 b dC D d  2 dC 
= r
r2 dr r2 dr dr

KP0 b
Introducing the dummy variable A = D to make things easier and then expanding the RHS:
dC dC d2 C
A = 2r + r2 2
dr dr dr
d2 C dC  A 2
=
dr2 dr r2 r

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 dC
Then, letting B = dr ,

dB A 2
=B 2
dr r r
A
ln(B) = 2ln(r) + a3
r
dC h A i 1 h Ai
B= = exp 2ln(r) + a3 = 2 exp a3
dr r r r

A
Next, letting u = a3 r, because Im lazy, and separating variables (again), we can finally get
an expression for C:
du A
= 2
dr r
1 r2
Z Z Z
1
dC = exp(u)dr = exp(u)du
r2 r2 A
1 D h KP0 b i
C = exp(u) + a4 = exp a3 + a4
A KP0 b Dr
Where a3 and a4 are of course integration constants.
(d) And then we can apply the boundary conditions to solve for a3 and a4 and do some rearrange-
ment to get an expression for C(r):

D h KP0 i
C(b) = C0 = exp a3 + a4
KP0 b D
h KP b i KP
0 0
a3 = ln (C0 a4 ) +
D D
h KP b i
0
C(r) = (C0 a4 )exp (1 ) + a4
D r
 KP 
0
C() = 0 = (C0 a4)exp + a4
D
C0 exp( KP
D )
0
a4 =
1 exp( KP
D )
0

 exp( KP
D )
0  h KP
0 b i C0 exp( KP
D )
0
C(r) = C0 1 + exp (1 )
1 exp( KP
D )
0 D r 1 exp( KP
D )
0

C0 h KP0 b i  KP 
0
C(r) = KP0
exp( (1 )) exp
1 exp( D ) D r D

Well. Wasnt that invigorating!

4. Comparing flow in human vs. rabbit aortas, noting that cardiac output is Q, heart rate is 1/,
recalling that rz = P R
2L , and making sure we have the right units:

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 Human Rabbit
Q (ml/s) 83.3 5
(1/s) 1.2 3.3
D (cm) 2.5 3
(cm2 /s) 0.04 0.04
(dyn/cm2 ) 2.2 75
v (cm/s) 17 71
Re 1061 531
6.8 1.4
We see that the human and rabbit are fairly similar w.r.t. Re, though maybe more different in and
.
5. As you probably noted (since the first thing you did was to plot those values, right?), the relationship
is not linear. Using the tube area of 3.14 cm2 , = 0.01 cm2 /sm velocities and Reynolds numbers
Q
can be calculated (see table). If we look at P/L , we see that for the first two values, they are almost
the same and also that Re is relatively low. However, for the third value, we have moved into a
region of transition flow moving towards turbulent flow. In this regime we do not expect Poiseuille
flow because this solution was developed for laminar flow.
Q
P (g/cm.s2 ) L (cm) Q (cm3 /s) v (cm/s) Re P/L (g/cm2 .s2 ) P/L
1.5 5 12 3.8 764 0.3 40
3.8 5 30 9.5 1910 0.76 39.5
12 5 55 17.5 3501 2.4 22.9